Mentions:
We subjected Col1a2CreERT:R26RtdTomato mice to ischemia-reperfusion cardiac injury 5 days following cessation of tamoxifen injection. By day 3 post-injury, 35±3% (mean±S.E.M) of labeled cardiac fibroblasts in the region of injury expressed the endothelial specific marker VECAD, while in sham injured animals only rare labeled cells expressed VECAD (<0.3%) (Fig. 1a–c). Approximately 24±4%, 44±4% and 35±3% (mean±S.E.M) of labeled cardiac fibroblasts also expressed other endothelial markers such as endothelial nitric oxide synthase (eNOS) and the endothelial tight junctional proteins Claudin 514 and Occludin14 respectively (Fig. 1a–c). MEndoT was most pronounced in the injury border zone significantly decreasing in regions remote from the infarct. (Fig. 1c). The fraction of cardiac fibroblasts expressing VECAD increased between 1 and 3 days post-injury and remained similar at 3, 7 and 14 days (Fig. 1d). The fraction of tdTomato positive cells expressing VECAD in sham injured animals at 3, 7 and 14 days was 0.3±0.1%, 1.4±1.4% and 0.6±0.4% (mean±S.E.M., p>0.05, one way Anova) demonstrating no temporal difference in the fraction of tdTomato labeled cells expressing VECAD following sham injury.

Mentions:
We subjected Col1a2CreERT:R26RtdTomato mice to ischemia-reperfusion cardiac injury 5 days following cessation of tamoxifen injection. By day 3 post-injury, 35±3% (mean±S.E.M) of labeled cardiac fibroblasts in the region of injury expressed the endothelial specific marker VECAD, while in sham injured animals only rare labeled cells expressed VECAD (<0.3%) (Fig. 1a–c). Approximately 24±4%, 44±4% and 35±3% (mean±S.E.M) of labeled cardiac fibroblasts also expressed other endothelial markers such as endothelial nitric oxide synthase (eNOS) and the endothelial tight junctional proteins Claudin 514 and Occludin14 respectively (Fig. 1a–c). MEndoT was most pronounced in the injury border zone significantly decreasing in regions remote from the infarct. (Fig. 1c). The fraction of cardiac fibroblasts expressing VECAD increased between 1 and 3 days post-injury and remained similar at 3, 7 and 14 days (Fig. 1d). The fraction of tdTomato positive cells expressing VECAD in sham injured animals at 3, 7 and 14 days was 0.3±0.1%, 1.4±1.4% and 0.6±0.4% (mean±S.E.M., p>0.05, one way Anova) demonstrating no temporal difference in the fraction of tdTomato labeled cells expressing VECAD following sham injury.

Bottom Line:
We show that the transcription factor p53 regulates such a switch in cardiac fibroblast fate.Loss of p53 in cardiac fibroblasts severely decreases the formation of fibroblast-derived endothelial cells, reduces post-infarct vascular density and worsens cardiac function.These observations demonstrate that mesenchymal-to-endothelial transition contributes to neovascularization of the injured heart and represents a potential therapeutic target for enhancing cardiac repair.